Transcription Program of Murine Gammaherpesvirus 68

Transcription Program of Murine Gammaherpesvirus 68

Transcription Program of Murine Gammaherpesvirus 68
Dendritic cells (DCs) play a central role in initiating adaptive immunity. These glycoproteins are thought to be involved in cell binding, but little is known of the roles they might play in the whole viral replication cycle. Murine gammaherpesvirus γHV68 is genetically and biologically related to human gammaherpesviruses and herpesvirus saimiri and has been reported to be associated with lymphoproliferative disease in mice (N. While in vitro growth of these mutant viruses was unaffected, lytic replication in the lungs following low-dose intranasal inoculation was attenuated for both mutants deficient in CDK binding as well as virus in which the entire v-cyclin open reading frame was disrupted by the insertion of a translation termination codon. In order to define the domains of RTA responsible for their functional differences in viral promoter activation and initiation of the MHV-68 lytic cycle, chimeric RTA proteins were constructed by exchanging the N-terminal and C-terminal domains of the RTA proteins. Shimizu, S. We determined that the transcription profiles at the peak of lytic gene expression are similar in cultured fibroblast and in the lung of infected mice.

Mutagenesis studies have further characterized the nucleotides important for mediating RTA binding by an EMSA. The recombinant virus replicates faster then the parental strain and the DNA arrays revealed that nearly every MHV-68 ORF examined was activated by RTA overexpression. Early functional analyses established M1 as a candidate latency-associated gene product critical for regulating reactivation from latently infected peritoneal macrophages, as well as promotion of MHV68-associated multiorgan fibrosis in mice lacking the gamma interferon (IFN-γ) receptor (IFN-γR) (8, 9).

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